Characterization of Tandem Repeat and Structural Variants Contributing to Addictive Behaviors in Mice and Rats

Study title

Characterization of Tandem Repeat and Structural Variants Contributing to Addictive Behaviors in Mice and Rats

Description

This study will generate the first large-scale resource for analyzing the effects of complex variation on mouse and rat phenotypes. We use this resource to examine gene expression and behavioral traits in inbred mice (BXD recombinant inbred strains, the Hybrid Mouse Diversity Panel (HMDP), the Diversity Outbred (DO) mice, the Hybrid Rat Diversity Panel (HRDP) and the Heterogeneous Stock (HS) outbred rats. In Specific Aim 1 we will characterize SVs in inbred and outbred mice and rats by single-molecule sequencing. In Specific Aim 2 we will genotype TR in inbred and outbred mice and rats. Finally, in Specific Aim 3 we will perform GWAS using SV and TR for gene expression and behavioral traits. We will determine the phenotypic consequences of the SV and TR genotypes on gene expression and behavioral traits. We will impute SVs and TRs into outbred mice and rats and then perform GWAS using the wealth of preexisting gene expression and behavioral data that are available for the mouse and rat populations studied in this project. Completion of this project will characterize the SV and TR landscape in mice and rats, elucidate their role in gene expression and complex behavioral traits relevant to addiction, and create a community resource that will enhance numerous ongoing mouse and rat genetic studies.

Funding sources

U01DA051234

Methods for genotype

low-coverage WGS based on Riptide library preparation (pulication in progress)

Methods for Phenotypes

long access oxycodone self-administration;

short access oxycodone self-administration;

progressive ratio task;

irritability;

Methods for Omics

NaN

Data Freezes

NaN